ABSTRACT
Organoids are three-dimensional (3D) biological structures constructed in vitro by stem cells, which partially mimic the function of real organs. Brain organoids are an extremely important branch of organoid research. This technology can differentiate pluripotent stem cells into the required cell types in a 3D culture environment, and self-assemble into structural bodies, but it is currently unable to fully replicate the structural and physiological features of the real human brain. The maturity of brain organoids may form consciousness, which poses ethical issues such as determining moral status and informed consent in brain organoids research. This paper elaborated on the research progress and future development direction of brain organoids, and proposed multidimensional governance strategies for ethical issues faced in brain organoids research from the perspectives of ethical principles, ensuring public informed consent, and legal supervision. By exploring the above issues, reference will be provided for formulating ethical principles to guide the research and application of brain organoids in the future.
ABSTRACT
<p><b>BACKGROUND</b>Hyperglycemia may accelerate liver fibrosis. Currently, there is no effective treatment for liver fibrosis induced by type 2 diabetes. The study aim was to investigate whether RhoA/Rho kinase (ROCK) pathway is involved in liver fibrosis in the rats with type 2 diabetes and define the protective effects of fasudil on livers.</p><p><b>METHODS</b>A rat model of type 2 diabetes was established by high fat diet combined with streptozotocin (30 mg/kg, intraperitoneal injection). Animals were randomly assigned to 3 groups: control rats, untreated diabetic rats that received vehicle and fasudil-treated diabetic rats that received ROCK inhibitor fasudil hydrochloride hydrate (10 mg/kg per day, intraperitoneal injection, for 14 weeks). The morphological features of liver were observed by HE staining. Accumulation of collagen in livers was determined by Masson staining and the measurement of hydroxyproline. The mRNA expression of transforming growth factor-β1 (TGFβ1), connective tissue growth factor (CTGF), type-I, and type-III procollagen was assessed with real-time polymerase chain reaction. The phosphorylation of myosin phosphatase target subunit-1 (MYPT1) and the protein levels of TGFβ1 and α-smooth muscle actin (a-SMA) were evaluated by Western blotting.</p><p><b>RESULTS</b>Compared with control rats, untreated diabetic rats showed higher values of collagen and hydroxyproline in livers (P < 0.01), the phosphorylation of MYPT1 and the protein levels of TGFβ1 and α-SMA were increased (P < 0.01), and the mRNA expression of TGFβ1, CTGF, type-I, and type-III procollagen was upregulated (P < 0.01); compared with untreated diabetic rats, treatment with fasudil signifcantly reduced values of collagen and hydroxyproline (P < 0.01), and decreased the phosphorylation of MYPT1 and the levels of TGFβ1 and α-SMA (P < 0.01), concomitant with the downregulation of TGFβ1/CTGF, type-I, and type-III procollagen mRNA expression (P < 0.01).</p><p><b>CONCLUSIONS</b>Fasudil ameliorates liver fibrosis in rats with type 2 diabetes at least partly by inhibiting TGFβ1/CTGF pathway and α-SMA expression. Inhibition of RhoA/ROCK may be a novel therapeutic target for liver fibrosis in diabetic non-alcoholic steatohepatitis.</p>
Subject(s)
Animals , Female , Rats , 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine , Therapeutic Uses , Connective Tissue Growth Factor , Metabolism , Diabetes Mellitus, Type 2 , Drug Therapy , Liver Cirrhosis , Drug Therapy , Metabolism , Protein Kinase Inhibitors , Therapeutic Uses , Rats, Sprague-Dawley , Transforming Growth Factor beta1 , Metabolism , rho-Associated KinasesABSTRACT
AIM: To investigate the therapeutic effects of Zhuyejiao tablets (Tab.ZYJ) on chronic pelvic inflammation (CPI) induced by coliform in rats. METHODS: The CPI model was made by injecting coliform O-B_4 standard strains in the uterus of rat. Animals were randomly divided into six groups and drugs were administered for 21 days, bid, respectively. The immune function of animals was measured and the uterus was pathologically observed. RESULTS: The level of serum agglutinin and lymphocyte transformation index markedly increased in all ZYJ groups. Morphological investigation also revealed the alleviation of inflammation in ZYJ groups. CONCLUTION: ZYJ has therapeutic effects on chronic pelvic inflammation in rats.